ABSTRACT Oral disease, in particular childhood caries, remains a major health burden which affects some communities disproportionally, including regions of Appalachia. Both increased sugar intake and frequency of exposure alter the oral microbial community, triggering a disease process that leads to caries. Additional factors associated with caries in children include genetic risk, household SES, maternal caregiving behavior and stress, access to care. Progress has been made in understanding many of these factors. However, much remains to be done in order to further characterize individual risk factors, but just as importantly, to determine how interactions between them lead to oral health disparities. The current proposal is a renewal of our ongoing project (R01-DE-014899) to identify factors contributing to the oral health disparity seen in northern Appalachia. The guiding philosophy of our project (the Center for Oral Health Research in Appalachia; COHRA) has been and continues to be that developing strategies to address this disparity requires simultaneous study of multiple risk components (ideally within families) to determine their roles, interactions among them, and their transmissibility patterns. COHRA's long- term goal remains to determine the sources of oral health disparity in a high risk, Northern Appalachian population so that effective preventive interventions can be designed and targeted. During the previous project period that began Sept 1, 2009, we recruited a cohort of approximately 1000 northern Appalachian women during pregnancy (COHRA2), following them and their children through their children's second birthday. This prospective study of mother-child pairs complements the original cohort of approximately 840 northern Appalachian families (COHRA1) by gathering multifaceted, longitudinal data on the earliest antecedents of caries formation. As detailed in the progress report, the specific aims of the previous project period (using both COHRA1 and COHRA2 cohorts) were all accomplished (recruitment targets, genetic analyses of the COHRA1 cohort, psychosocial investigations, microbial assessments). We propose to follow the current COHRA2 cohort as it grows from ages 2 to 6, and to use the resulting longitudinal demographic, medical, diet, and psychosocial data to test hypotheses about the causal relationships between risk factors contributing to the unusually high rates of caries formation in this population. We will integrate the additional data to be collected with existing and new genetic and microbial data to identify ?cariogenic profiles,? in which the interactions between mother and child genetics, oral ecology, diet, and other environmental/psychosocial behaviors in infancy and early childhood are combined to predict unusually high risks for onset of caries before age 6.